Folk moral relativism

It has often been suggested that people’s ordinary folk understanding of morality involves a rejection of moral relativism and a belief in objective moral truths. The results of six studies call this claim into question. Participants did offer apparently objectivist intuitions when confronted with questions about individuals from their own culture, but they offered increasingly relativist intuitions as they were confronted with questions about individuals from increasingly different cultures or ways of life. In light of these data, the authors hypothesize that people do not have a fixed commitment to moral objectivism but instead tend to adopt different views depending on the degree to which they consider radically different perspectives on moral questions. [NOTE: This is a reprint of Sarkissian et al 2011

Changing the direction of environmental investment in Australia: Learnings from implementing INFFER

Investment in natural resource management (NRM) by regional organisations in Australia has been widely criticised for failing to achieve substantial environmental outcomes. The Investment Framework for Environmental Resources (INFFER) is a tool for developing and prioritising projects to address environmental issues such as water quality, biodiversity decline, environmental pest impacts and land degradation. INFFER is an asset-based, targeted, and outcome-focussed approach to environmental investment, and as such is a very different and more rigorous approach to prioritising possible environmental projects than used previously by most catchment management organisations (CMOs) in Australia. From 2008 to 2010 INFFER has been trialled with CMOs. Evaluation and benchmarking data obtained at 2-day INFFER training sessions with seven CMOs in three eastern Australia states are reported. Before commencing to use INFFER, CMO staff are generally confident about the current decision-making processes for environmental investment used within their organisation. In some cases, this initial perception challenges their acceptance of a new approach to investment decisionmaking. Key issues when implementing INFFER include concerns about changing the direction of CMO investment, concerns about compatibility with funder requirements, and various issues associated with specific aspects of the Framework. Perceived complexity of INFFER, existing institutional arrangements, and the legacy of past institutional arrangements remain serious barriers to the adoption of methods to improve environmental outcomes from NRM investment. Despite these difficulties INFFER is being used by a number of CMOs. However, it is likely that widespread adoption of INFFER, or indeed any other transparent and robust process, will only occur with greater requirement from governments for environmental decision making by regional NRM bodies that is more focused on outcomes and cost-effectiveness.NRM investment planning, NRM investment prioritisation, regional catchment management organisations, NRM policy, environmental planning, environmental prioritisation, environmental policy, Environmental Economics and Policy, Research and Development/Tech Change/Emerging Technologies, Q50, Q58,

Teacher Observations Using Telepresence Robots: Benefits and Challenges for Strengthening Evaluations

Project SCOUT (School Classroom Observations Using Telepresence) details findings from a pilot project where observers used a telepresence robot designed to capture teaching episodes. The study examined: 1) participants’ ability to review classroom teaching and determine teaching quality using a telepresence format; 2) whether a telepresence robot allowed observers to review the specific teaching competencies they would otherwise evaluate during in-person observations; and 3) the success of the telepresence robot in evaluating specific pedagogical environments (i.e., Montessori classrooms). Survey and observation data from two focal classrooms highlight the benefits of telepresence tools by allowing flexibility and the potential for a wider audience of observers using real time data collection. Limitations of a telepresence robot include challenges in its ability to capture classroom nuances necessary for evaluation, coaching, or supervisory support. Those who use a telepresence robot must be particularly sensitive to using a technology that might cause privacy and safety concerns for children and their families, particularly for marginalized communities

A murine herpesvirus closely related to ubiquitous human herpesviruses causes T-cell depletion

ABSTRACT The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4 + T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7. IMPORTANCE Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and clinical ramifications of roseolovirus infection in humans have been hypothesized, but studies showing definitive causative relationships between infection and disease susceptibility are lacking. Here we show that MRV infects the thymus and causes T-cell depletion, suggesting that other roseoloviruses may have similar properties. </jats:p

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

Conditional degradation of SDE2 by the Arg/N-End rule pathway regulates stress response at replication forks

Multiple pathways counteract DNA replication stress to prevent genomic instability and tumorigenesis. The recently identified human SDE2 is a genome surveillance protein regulated by PCNA, a DNA clamp and processivity factor at replication forks. Here, we show that SDE2 cleavage after its ubiquitin-like domain generates Lys-SDE2^(Ct), the C-terminal SDE2 fragment bearing an N-terminal Lys residue. Lys-SDE2^(Ct) constitutes a short-lived physiological substrate of the Arg/N-end rule proteolytic pathway, in which UBR1 and UBR2 ubiquitin ligases mediate the degradation. The Arg/N-end rule and VCP/p97^(UFD1-NPL4) segregase cooperate to promote phosphorylation-dependent, chromatin-associated Lys-SDE2^(Ct) degradation upon UVC damage. Conversely, cells expressing the degradation-refractory K78V mutant, Val-SDE2^(Ct), fail to induce RPA phosphorylation and single-stranded DNA formation, leading to defects in PCNA-dependent DNA damage bypass and stalled fork recovery. Together, our study elucidates a previously unappreciated axis connecting the Arg/N-end rule and the p97-mediated proteolysis with the replication stress response, working together to preserve replication fork integrity

Parents’ Communication Work in the Management of Food Allergies

The National Academies of Sciences, Engineering, and Medicine (NASEM) has identified food allergies as a critical public health issue that significantly affects quality of life for patients and their families. Despite the crisis-level status of food allergies, especially in children, there are currently no curative treatments. As a result, impacted families must learn how to carry the burden of disease management. Using an expanded application of the concept of communication work, this study features data from interviews with 26 parents of food allergic children and explores how parents navigate the nuances of food allergy maintenance while negotiating and preserving valued relationships and identities through everyday talk. Results revealed that parents used communication to legitimate food allergy, balance potential face-threats with identity and relational goals, and coordinate care with spouses. Due to the lack of therapeutic treatment options, we found that parents utilize communication work, which is both demanding and effortful, as a form of disease management.This project was funded by a Grant Improvement through Faculty Training (GIFT) award, sponsored by the School of Liberal Arts and the Office of the Vice Chancellor for Research at IUPUI. We would like to thank the food allergy parents who generously shared their stories with us

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density

\u27Living cantilever arrays\u27 for characterization of mass of single live cells in fluids

The size of a cell is a fundamental physiological property and is closely regulated by various environmental and genetic factors. Optical or confocal microscopy can be used to measure the dimensions of adherent cells, and Coulter counter or flow cytometry ( forward scattering light intensity) can be used to estimate the volume of single cells in a flow. Although these methods could be used to obtain the mass of single live cells, no method suitable for directly measuring the mass of single adherent cells without detaching them from the surface is currently available. We report the design, fabrication, and testing of \u27living cantilever arrays\u27, an approach to measure the mass of single adherent live cells in fluid using silicon cantilever mass sensor. HeLa cells were injected into microfluidic channels with a linear array of functionalized silicon cantilevers and the cells were subsequently captured on the cantilevers with positive dielectrophoresis. The captured cells were then cultured on the cantilevers in a microfluidic environment and the resonant frequencies of the cantilevers were measured. The mass of a single HeLa cell was extracted from the resonance frequency shift of the cantilever and was found to be close to the mass value calculated from the cell density from the literature and the cell volume obtained from confocal microscopy. This approach can provide a new method for mass measurement of a single adherent cell in its physiological condition in a non-invasive manner, as well as optical observations of the same cell. We believe this technology would be very valuable for single cell time-course studies of adherent live cells

Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains &gt;25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling